Dyspnoea and worsening heart failure in patients with acute heart failure: results from the Pre-RELAX-AHF study

Although dyspnoea is the most common cause of admission for acute heart failure (AHF), more needs to be known about its clinical course and prognostic significance. The Pre-RELAX-AHF study randomized 232 subjects with AHF to placebo or four doses of relaxin and evaluated early (6-24 h Likert scale) and persistent [change in visual analogue scale area under the curve (VAS AUC) through Day 5] dyspnoea relief. Worsening heart failure (WHF) was defined as worsening AHF signs and symptoms requiring additional therapy. Patients were followed until Day 180. Early dyspnoea relief was observed in only 25% of all patients, and VAS AUC at 5 days was 45% over baseline values in all patients (32% placebo; 50% all relaxin-treated patients). Worsening heart failure to Day 5 was observed in 16% of all patients (21% placebo; 14% relaxin). Lack of persistent dyspnoea relief and WHF were associated with a longer length of initial hospital stay and worse 60-day outcomes. Dyspnoea relief in patients admitted with AHF is often incomplete, and many may show WHF after the initial stabilization. Both lack of persistent dyspnoea relief and in-hospital WHF predict a longer length of stay and worse outcome

Transient up- and down-regulation of expression of myosin light chain 2 and myostatin mRNA mark the changes from stratified hyperplasia to muscle fiber hypertrophy in larvae of gilthead sea bream (Sparus aurata L.)

Hyperplasia and hypertrophy are the two mechanisms by which muscle develops and grows. We study these two mechanisms, during the early development of white muscle in Sparus aurata, by means of histology and the expression of structural and regulatory genes. A clear stage of stratified hyperplasia was identified early in the development of gilthead sea bream but ceased by 35 dph when hypertrophy took over. Mosaic recruitment of new white fibers began as soon as 60 dph. The genes mlc2a and mlc2b were expressed at various levels during the main phases of hyperplasia and hypertrophy. The genes myog and mlc2a were significantly up-regulated during the intensive stratified formation of new fibers and their expression was significantly correlated. Expression of mstn1 and igf1 increased at 35 dph, appeared to regulate the hyperplasia-to-hypertrophy transition, and may have stimulated the expression of mlc2a, mlc2b and col1a1 at the onset of mosaic hyperplasia. The up-regulation of mstn1 at transitional phases in muscle development indicates a dual regulatory role of myostatin in fish larval muscle growth

Of mongooses and mitigation: ecological analogues to geoengineering

Anthropogenic global warming is a growing environmental problem resulting from unintentional human intervention in the global climate system. If employed as a response strategy, geoengineering would represent an additional intentional human intervention in the climate system, with the intent of decreasing net climate impacts. There is a rich and fascinating history of human intervention in environmental systems, with many specific examples from ecology of deliberate human intervention aimed at correcting or decreasing the impact of previous unintentionally created problems. Additional interventions do not always bring the intended results, and in many cases there is evidence that net impacts have increased with the degree of human intervention. In this letter, we report some of the examples in the scientific literature that have documented such human interventions in environmental systems, which may serve as analogues to geoengineering. We argue that a high degree of system understanding is required for increased intervention to lead to decreased impacts. Given our current level of understanding of the climate system, it is likely that the result of at least some geoengineering efforts would follow previous ecological examples where increased human intervention has led to an overall increase in negative environmental consequences

Lung MRI with hyperpolarised gases : current & future clinical perspectives

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique – hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe – a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases

The Peripheral Arterial disease study (PERART/ARTPER): prevalence and risk factors in the general population

<p>Abstract</p> <p>Background</p> <p>The early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the study is to know the prevalence and associated risk factors of peripheral arterial disease in the general population.</p> <p>Methods</p> <p>We performed a cross-sectional, multicentre, population-based study in 3786 individuals >49 years, randomly selected in 28 primary care centres in Barcelona (Spain). Peripheral arterial disease was evaluated using the ankle-arm index. Values < 0.9 were considered as peripheral arterial disease.</p> <p>Results</p> <p>The prevalence (95% confidence interval) of peripheral arterial disease was 7.6% (6.7-8.4), (males 10.2% (9.2-11.2), females 5.3% (4.6-6.0); <it>p </it>< 0.001).</p> <p>Multivariate analysis showed the following risk factors: male sex [odds ratio (OR) 1.62; 95% confidence interval 1.01-2.59]; age OR 2.00 per 10 years (1.64-2.44); inability to perform physical activity [OR 1.77 (1.17-2.68) for mild limitation to OR 7.08 (2.61-19.16) for breathless performing any activity]; smoking [OR 2.19 (1.34-3.58) for former smokers and OR 3.83 (2.23-6.58) for current smokers]; hypertension OR 1.85 (1.29-2.65); diabetes OR 2.01 (1.42-2.83); previous cardiovascular disease OR 2.19 (1.52-3.15); hypercholesterolemia OR 1.55 (1.11-2.18); hypertriglyceridemia OR 1.55 (1.10-2.19). Body mass index ≥25 Kg/m²OR 0.57 (0.38-0.87) and walking >7 hours/week OR 0.67 (0.49-0.94) were found as protector factors.</p> <p>Conclusions</p> <p>The prevalence of peripheral arterial disease is low, higher in males and increases with age in both sexes. In addition to previously described risk factors we found a protector effect in physical exercise and overweight.</p

Complementary and alternative medicine for patients with chronic fatigue syndrome: A systematic review

<p>Abstract</p> <p>Background</p> <p>Throughout the world, patients with chronic diseases/illnesses use complementary and alternative medicines (CAM). The use of CAM is also substantial among patients with diseases/illnesses of unknown aetiology. Chronic fatigue syndrome (CFS), also termed myalgic encephalomyelitis (ME), is no exception. Hence, a systematic review of randomised controlled trials of CAM treatments in patients with CFS/ME was undertaken to summarise the existing evidence from RCTs of CAM treatments in this patient population.</p> <p>Methods</p> <p>Seventeen data sources were searched up to 13th August 2011. All randomised controlled trials (RCTs) of any type of CAM therapy used for treating CFS were included, with the exception of acupuncture and complex herbal medicines; studies were included regardless of blinding. Controlled clinical trials, uncontrolled observational studies, and case studies were excluded.</p> <p>Results</p> <p>A total of 26 RCTs, which included 3,273 participants, met our inclusion criteria. The CAM therapy from the RCTs included the following: mind-body medicine, distant healing, massage, tuina and tai chi, homeopathy, ginseng, and dietary supplementation. Studies of qigong, massage and tuina were demonstrated to have positive effects, whereas distant healing failed to do so. Compared with placebo, homeopathy also had insufficient evidence of symptom improvement in CFS. Seventeen studies tested supplements for CFS. Most of the supplements failed to show beneficial effects for CFS, with the exception of NADH and magnesium.</p> <p>Conclusions</p> <p>The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted.</p

Planck 2015 results. XVIII. Background geometry and topology of the Universe

Maps of cosmic microwave background (CMB) temperature and polarization from the 2015 release of Planck data provide the highestquality full-sky view of the surface of last scattering available to date. This enables us to detect possible departures from a globally isotropic cosmology. We present the first searches using CMB polarization for correlations induced by a possible non-trivial topology with a fundamental domain that intersects, or nearly intersects, the last-scattering surface (at comoving distance χrec), both via a direct scan for matched circular patterns at the intersections and by an optimal likelihood calculation for specific topologies. We specialize to flat spaces with cubic toroidal (T3) and slab (T1) topologies, finding that explicit searches for the latter are sensitive to other topologies with antipodal symmetry. These searches yield no detection of a compact topology with a scale below the diameter of the last-scattering surface. The limits on the radius ℛi of the largest sphere inscribed in the fundamental domain (at log-likelihood ratio Δlnℒ > −5 relative to a simply-connected flat Planck best-fit model) are: ℛi > 0.97 χrec for the T3 cubic torus; and ℛi > 0.56 χrec for the T1 slab. The limit for the T3 cubic torus from the matched-circles search is numerically equivalent, ℛi > 0.97 χrec at 99% confidence level from polarization data alone. We also perform a Bayesian search for an anisotropic global Bianchi VIIh geometry. In the non-physical setting, where the Bianchi cosmology is decoupled from the standard cosmology, Planck temperature data favour the inclusion of a Bianchi component with a Bayes factor of at least 2.3 units of log-evidence. However, the cosmological parameters that generate this pattern are in strong disagreement with those found from CMB anisotropy data alone. Fitting the induced polarization pattern for this model to the Planck data requires an amplitude of −0.10 ± 0.04 compared to the value of + 1 if the model were to be correct. In the physically motivated setting, where the Bianchi parameters are coupled and fitted simultaneously with the standard cosmological parameters, we find no evidence for a Bianchi VIIh cosmology and constrain the vorticity of such models to (ω/H)0 < 7.6 × 10-10 (95% CL)